Prostate cancer will soon become the leading cause of cancer death of men in the United States. One-third of men over 50 will develop prostate cancer at some time in their lives. In 1992, nearly 132,000 men will be diagnosed as having prostate cancer, and 34,000 are likely to die from the disease. With the aging U.S. population, it has been estimated that prostate cancer cases will increase 90% and deaths will increase 37% by the end of the decade.
There are two main types of prostate cancer: sarcoma, a rare, highly malignant and fast growing tumor; and adenocarcinoma, a slower growing type which comprises 95% of prostate cancers. Adenocarcinoma is often devoid of symptoms in its early stages, when it is most susceptible to treatment. Unfortunately, 40% of adenocarcinomas are detected at an advanced stage.
Among the methods employed for detection of prostate cancer, the digital rectal exam is the oldest and simplest, but in 70% of patients the exam fails to reveal cancer until it has spread to other parts of the body. Because of the high miss rate, such exams are now being used in conjunction with a blood test for prostate specific antigen (PSA), which was first isolated in 1979. PSA is recognized as the best tumor marker presently available, being more sensitive and more specific than either the rectal exam or the prostatic acid phosphatase test. The PSA protein is made and secreted by both normal and cancerous prostate cells, but is elevated in the blood of men with prostate cancer. The older prostatic acid phosphatase (PAP) test has been displaced by the PSA assay, although it remains a tool for monitoring metastases and response to therapy, especially endocrine treatment.
Once diagnosed, there are three basic treatment options for prostate cancer: surgery, radiation and endocrine therapy. Prostate cancer is resistant to most of the commonly used anticancer drugs, including cisplatin, adriamycin and cyclophosphamide. The choice of treatment depends primarily on the stage of the disease. As with other solid tumors, surgery is preferred when it is feasible. If pelvic lymph nodes reveal cancerous invasion, radical surgery or radiation are of little use.
Endocrine therapy, including diminishing the levels of testosterone by orchiectomy, is generally reserved for metastatic cancer and is not curative but only a means of slowing the progress of the disease. Prostatic carcinomas usually further metastasize to bone, where they are inaccessible to surgery and may be extremely painful to the patient.
New approaches to the treatment and diagnosis of prostate cancer are clearly and urgently needed. While the PSA protein is a useful diagnostic marker, antibodies to PSA are not useful for therapy or imaging of prostate cancer metastases because the antigen is not a cell membrane protein. Monoclonal antibodies have been isolated that react with normal prostate cells, malignant prostate cells or proteins present in prostate secretions (1-8). Monoclonal antibodies P25.48 (Bazinet et al., Cancer Res. 48:6938-6942 (1988)), P25.91 (Bazinet et al., Cancer Res. 48:6938-6942 (1988)), MCA/R1 and LSD 83/21 (Starling and Wright, Cancer Res. 45:804-808 (1985)) do not react at all with normal prostate cells, and monoclonal antibody PD41 (Beckett, Cancer Res. 51:1326-1333 (1991)) reacts with less than 1% of epithelial cells in normal prostate. Antibodies HNK-1 and TURP-27 recognize neural cell adhesion molecules that are also expressed in normal prostate. However, these antibodies only react with scattered cells in the normal prostate epithelium. In addition, monoclonal antibodies HNK-1 and TURP-27 react with normal brain tissue. Monoclonal antibody PR92 was produced by immunizing with cells from a long established prostate cell line, DU145 cells, with which it strongly reacts (Kim et al., Cancer Res. 48:4543-4548 (1988)). The DU145 cells may lack certain antigens characteristic of prostate cells. Horoszewicz et al. (Anticancer Res. 7:927-936 (1987)) have developed a monoclonal antibody (7E11-C5) to prostate cancer cells by immunizing mice with the cell line LNCaP. This antibody, however, reacts uniformly with LNCaP cells and skeletal and cardiac muscle (Horoszewicz et al., ibid., and Lopes et al., Cancer Res. 50:6423-6429 (1990)).
Quite surprisingly, the present invention provides a novel approach to solving the need for improved treatment and diagnosis of prostate cancer, and fulfills other related needs.